Dataset Information

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol.

ABSTRACT:

Trial design

We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.

Methods

The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52?weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study.

Conclusions

There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.

Trial registration

Current Controlled Trials, ID: ISRCTN46017566 . Registered on 4 July 2014.

SUBMITTER: Al-Laith M

PROVIDER: S-EPMC6633323 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol.

Al-Laith Mariam M Jasenecova Marianna M Abraham Sonya S Bosworth Aisla A Bruce Ian N IN Buckley Christopher D CD Ciurtin Coziana C D'Agostino Maria-Antonietta MA Emery Paul P Gaston Hill H Isaacs John D JD Filer Andrew A Fisher Benjamin A BA Huizinga Thomas W J TWJ Ho Pauline P Jacklin Clare C Lempp Heidi H McInnes Iain B IB Pratt Arthur G AG Östor Andrew A Raza Karim K Taylor Peter C PC van Schaardenburg Dirkjan D Shivapatham Dharshene D Wright Alison J AJ Vasconcelos Joana C JC Kelly Joanna J Murphy Caroline C Prevost A Toby AT Cope Andrew P AP

Trials 20190715 1

<h4>Trial design</h4>We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.<h4>Methods</h4>The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlan ...[more]

PMID: 31307535

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Project description:BackgroundThere is currently insufficient evidence on the safety and efficacy of antenatal corticosteroids in preventing mortality and severe morbidity amongst late preterm newborns in low-resource countries.MethodsWe conducted a double-blind, randomized trial in four hospitals in India between 26 December 2017 to 21 May 2020. Pregnant women at risk of imminent preterm birth between 34 weeks 0 days and 36 weeks 0 days of gestation were recruited. Women were randomly assigned (1:1) to a course of 6 mg intramuscular dexamethasone or an identical placebo. All trial participants, research staff and outcome assessors were masked to allocation. Primary outcomes were neonatal death, any baby death (stillbirth or neonatal death), severe neonatal respiratory distress and possible maternal bacterial infection. The study was registered with ANZCTR (ACTRN12617001494325) and CTRI (CTRI/2017/05/008721).FindingsWe randomized 782 women, 391 to each arm. Neonatal death occurred in 11 of 412 liveborn babies (2.7%) in the dexamethasone group and 12 of 425 liveborn babies (2.8%) in the placebo group (RR 0.95; 95% CI 0.42-2.12). Any baby death occurred in 16 of 417 infants (3.8%) in the dexamethasone group and 19 of 432 infants (4.4%) in the placebo group (RR 0.87; 95% CI 0.45-1.67). Severe neonatal respiratory distress was infrequent in both groups (0.8% vs 0.5%; RR 1.56; 95% CI 0.26-9.29). Possible maternal bacterial infection did not differ between groups (2.3% vs. 3.8%, RR 0.60; 95% CI 0.27-1.35). Fewer neonates in the dexamethasone group required resuscitation at birth (RR 0.38, CI 0.15-0.97). Other secondary outcomes were similar in the two arms. The trial was stopped due to lower than expected prevalence of primary outcomes and slow recruitment.InterpretationAntenatal dexamethasone did not result in a reduction in neonatal death, stillbirth or neonatal death, or severe neonatal respiratory distress in this trial. The overall trend of effects suggests that potential benefit of dexamethasone in late preterm cannot be excluded, and further trials are required.FundingThis trial was primarily funded by the Bill and Melinda Gates Foundation (Grant OPP1136821). Additional support was provided by UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research; and Department of Maternal, Newborn, Child, Adolescent Health, and Ageing, of the World Health Organization, Geneva, Switzerland.

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Dataset Information

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol.

Trial design

Methods

Conclusions

Trial registration

Publications

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol.

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